A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

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dc.contributor.authorChen, J.
dc.contributor.authorNeil, J.A.
dc.contributor.authorTan, J.P.
dc.contributor.authorRudraraju, R.
dc.contributor.authorMohenska, M.
dc.contributor.authorSun, Y.B.Y.
dc.contributor.authorWalters, E.
dc.contributor.authorBediaga, N.G.
dc.contributor.authorSun, G.
dc.contributor.authorZhou, Y.
dc.contributor.authorLi, Y.
dc.contributor.authorDrew, D.
dc.contributor.authorPymm, P.
dc.contributor.authorTham, W.H.
dc.contributor.authorRossello, F.J.
dc.contributor.authorNie, G.
dc.contributor.authorLiu, X.
dc.contributor.authorSubbarao, K.
dc.contributor.authorPolo, J.M.
dc.date.issued2023
dc.descriptionPublished online: 13 July 2023 Correction to: A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts (Nature Cell Biology, (2023), 25, 8, (1223-1234), 10.1038/s41556-023-01182-0), in the version of the article initially published, Y. Wang (RMIT University) was mistakenly omitted from the author list and contributions and has now been added in the HTML and PDF versions of the article.
dc.description.abstractSARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning SARS-CoV-2 infection during placentation and early pregnancy are not clear. Here, to shed light on this, we used induced trophoblast stem cells to generate an in vitro early placenta infection model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, we confirmed the ability of the virus to infect syncytiotrophoblasts through a previous endometrial cell infection. We further demonstrated transcriptional changes in infected syncytiotrophoblasts that led to impairment of cellular processes, reduced secretion of HCG hormone and morphological changes vital for syncytiotrophoblast function. Furthermore, different antibody strategies and antiviral drugs restore these impairments. In summary, we have established a scalable and tractable platform to study early placental cell types and highlighted its use in studying strategies to protect the placenta.
dc.description.statementofresponsibilityJ. Chen, J. A. Neil, J. P. Tan, R. Rudraraju, M. Mohenska, Y. B. Y. Sun, E. Walters, N. G. Bediaga, G. Sun, Y. Zhou, Y. Li, D. Drew, P. Pymm, W. H. Tham, F. J. Rossello, G. Nie, X. Liu, K. Subbarao and J. M. Polo
dc.identifier.citationNature Cell Biology, 2023; 25(8):1223-1234
dc.identifier.doi10.1038/s41556-023-01182-0
dc.identifier.issn1465-7392
dc.identifier.issn1476-4679
dc.identifier.orcidWalters, E. [0000-0002-4533-7884]
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/139124
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2004774
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1177174
dc.rights© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s41556-023-01182-0
dc.subjectTrophoblasts
dc.subjectPlacenta
dc.subjectHumans
dc.subjectCell Differentiation
dc.subjectPregnancy
dc.subjectFemale
dc.subjectCOVID-19
dc.subjectAngiotensin-Converting Enzyme 2
dc.subjectSARS-CoV-2
dc.titleA placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts
dc.typeJournal article
pubs.publication-statusPublished

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